: Optical coherence tomography (OCT) has evolved into a powerful microscopy technique for a broad range of applications in biology and clinical medicine. It can safely be used to image biological tissue with high resolution and can easily integrate flexible, narrow diameter optical fiber probes for imaging internal organs. Recent advances have increased OCT imaging speeds by nearly two orders of magnitude, enabling microscopic, three-dimensional imaging over large fields-of-view, a capability that cannot be provided by conventional imaging or histology. Viewed across the entire range of biological and clinical applications, the opportunity presented by OCT technology is immense. State-of-the-art OCT technology, however, is not widely available to the biological and clinical communities. The few commercial systems that are available don't integrate recent advances and don't permit customization to new biomedical applications. Additionally, the technical complexity of OCT is a barrier to implementation and innovation outside of a limited number of technical academic research groups and these groups have been focused on a narrow sector of the potential applications in biology and medicine. The overriding motivation of this proposed Resource is to address the deficient accessibility of cutting-edge OCT instrumentation and technology. We propose to meet this need through the innovation of new technical capabilities that are motivated by significant biological and clinical challenges, and through translation, facilitated by direct collaboration. To launch the Resource, we have initiated six driving biomedical projects (DBPs) and through extensive discussions have jointly identified specific technical projects that will have significant biological and clinical impact. Projects that could serve more than one DBP or that represented a synergistic combination were identified to be particularly attractive for the initial efforts of the Resource. The selected projects naturally fall into three core thematic areas: advanced structural imaging, functional and compositional contrast, and hybrid imaging modalities.